Antivirals Flashcards
What are the stages in viral infection?
- Binding
- Fusion & penetration
- Uncoating
- Translation
- Replication
- Assembly
- Budding & release
What are antiviral agents?
- They’re virustatic only; no cure.
- Main group targets: herpes, hepatitis, influenza viruses, HIV, ears-cov-2.
Describe the mechanism of action of drugs that inhibit the viral life cycle.
- Inhibitors of uncoating.
- Neuraminidase inhibitors
- Inhibitors of transcription.
- Inhibitors of RNA/DNA replication.
What is the MOA of Inhibitors of uncoating?
- Inhibit influenza A viral uncoating. Intracellular acidification is necessary for uncoating. Block viral proton channel (M2).
- High resistance rate, must be used in 2 days.
- ^ ADE: CNS effects, suicidal ideation, urinary retention.
- E.g. Amantadine & rimantadine.
*Can be used to tx Parkinson’s.
What is the MOA of Neuraminidase inhibitors?
- Specific inhibitors of influenza neuraminidase.
- Neuraminidase is important for viral release from cells.
- For influenza A & B in 1st 2 days.
- E.g Zanamivir (inhaler can cause bronco-spams) & Oseltamivir (orally- nausea).
What is the MOA of Inhibitors of transcription?
- Interferons (IFN) a&b but not gamma, induce a state of resistance to viral infection.
- Natural defense mechanism
What are the types of interferons?
- Type 1 IFN:
- IFNα, -β, and -ω.
- a-2(hep c) and a-2b used. ADE= flu-like symptoms, depression.
- Monomeric structure
- Induced by dsRNA anti-viral - Type 2:
- IFNγ is dimeric
- Produced by TH1 lymphocytes
What is the IFN receptor?
- Heterodimeric receptor
- IFNAR1/IFNAR2
- Tyrosine kinase receptor
- Binding activates gene expression
What are Inhibitors of DNA replication?
- Acyclic analogs of nucleotides.
- Intracellular phosphorylation to tri-phosphate.
- Compete with dGTP except cidofovir which competes for dCTP.
- Terminate DNA synthesis.
- E.g Acyclovir, Valacyclovir, Famciclovir.
- Used in heroes, shingles, chicken pox, CMV.
- ADE: Some neurotoxicity. Cidofovir is mutagenic & has many drug interactions.
What are Inhibitors of RNA replication?
Ribavirin:
- Nucleotide analogue
- Interferes with RNA synthesis
- Used in Hep c in conjunction with IFN, or in RSV and haemorrhagic fevers.
- ADE: haemolytic anemia
Describe the resistance of drugs that inhibit the viral life cycle.
- Inhibitors of uncoating: Resistance is due to mutations in M2 protein
What is HIV?
- From SIV infection of humans.
- Results in depletion of CD4+ T-cells.
- Leads to AIDS.
Describe the mechanism of action of reverse transcriptase inhibitors for treatment of HIV.
- Does not cure AIDS but stabilises the disease.
- NRT’s block reverse transcriptase (a HIV enzyme).
- HIV uses reverse transcriptase to convert its RNA into DNA (reverse transcription). Blocking reverse transcriptase and reverse transcription prevents HIV from replicating.
- Resistance: mutations in RT.
1. ADE of NRT’s: due to mitochondrial DNA polymerase inhibition (neuropathy, pancreatitis, myopathy).
Describe the mechanism of action of protease inhibitors for treatment of HIV.
- They block the enzyme “protease” which HIV cells need to develop and mature.
- Blocking protease prevents the virus from replicating. Protease inhibitors are a type of antiretroviral therapy (ART) medication.
- Resistance: mutations.
- E.g Ritonavir, Saquinavir.
- ADE: GI disturbance, Lipodystrophy, hyperlipidemia & insulin resistance.
How is drug resistance prevented?
- By using combination therapy.
